Stem cells are unique cell populations with the ability to undergo both renewal and differentiation. This fate choice is highly regulated by intrinsic signals and the external microenvironment. They can be identified in many adult mammalian tissues, such as bone marrow, skeletal muscle, skin and adipose tissue, where they contribute to replenishment of cells lost through normal cellular senescence or injury. Although stem cells in adult tissues may be capable of developing into more cell types than originally thought, they have a limited cellular regeneration or turnover.
Stem cells have been reported to exist during embryonic development and postnatally in bone marrow, skeletal muscle and skin. Embryonic stem (ES) cells are derived from the inner cell mass (ICM) at the blastula stage, and have the property of participating as totipotent cells when placed into host blastocysts. They are able not only to activate the expression of genes restricted to each of the three embryonic germ (EG) layers, but they are also able to express receptors for a number of different soluble growth factors with established effects on developmental pathways in vivo.
Adult stem cells, on the other hand, do not differentiate spontaneously, but can be induced to differentiate by applying appropriate growth conditions. Adult stem cells seem to be easier to maintain in culture than ES cells. Adult stem cells have the disadvantage of not being immortal, and most of them lose their pluripotency after a defined number of passages in culture. This short life-span may be a problem for clinical applications where a large amount of cells are needed.
In contrast to adult stem cells, ES cells, derived from blastocyst-stage early mammalian embryos, have the ability to give rise to cells that not only proliferate and replace themselves indefinitely, but that have the potential to form any cell type. ES cells tend to differentiate spontaneously into various types of tissues; however, specific growth induction conditions do not direct differentiation exclusively to specific cell types. Two reports describing the isolation, long-term culture, and differentiation of such cells have generated tremendous excitement in this regard and are herein incorporated by reference (Shamblott, Michael J., et al., “Derivation of Pluripotent Stem Cells from Cultured Human Primordial Germ Cells,” Proc. Natl. Acad. Sci. USA, Vol. 95, pp. 13726-31, November 1998; Thomson, James A., et al., “Embryonic Stem Cell Lines Derived from Human Blastocysts,” Science, Vol. 282, pp. 1145-47, Nov. 6, 1998). Although there is a great scientific interest in ES cell research, the destruction of embryos in order to harvest and experiment on ES cells still create unresolved ethical concerns.
Fetal tissue has been used in the past for autograft and allograft transplantation and tissue engineering research because of its pluripotency, proliferative ability and lack of immunogenecity. Fetal cells maintain a higher capacity to proliferate than adult cells and may preserve their pluripotency longer in culture. However, fetal cell transplants are plagued by problems that are very difficult to overcome. Fetal tissue can be currently obtained from a biopsy of the fetus itself during gestation or from cord blood at birth; however, both procedures are associated with a defined morbidity. Fetal tissue can also be obtained from aborted embryos, but this resource is limited. Beyond the ethical concerns regarding the use of cells from aborted fetuses or living fetuses, there are other issues which remain a challenge. For example, studies have shown that it generally takes about six fetuses to provide enough material to treat one patient with Parkinson's disease.
Because stem cells, particularly pluripotent stem cells appear to be an excellent resource for therapeutic applications, there is a great need for a source of stem cells that is plentiful, easy to manipulate, and avoids ethical considerations.